Hijack of ubiquitination by SARS-CoV-2 (WP4860)

Homo sapiens

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SARS-CoV-2 includes a novel Orf10 that interacts with muliple members of the Cullin 2 ubiquitin ligase complex as determined by AP-MS (Gordon 2020). The strongest interaction is with ZYG11B, a substrate adaptor for CUL2. By binding this complex, Orf10 might be able to hijack its activity. The hijacking of ubiquitination machinery is a common strategy of viruses to direct the degradation of viral restriction factors, for example. Also depicted here is the required neddylation (N8) of CUL2 by the NAE enzyme complex. The ability of this enzyme to transfer N8 to CUL2 is inhibited by the small molecule Pevonedistat.

Authors

Alex Pico , Egon Willighagen , Finterly Hu , Eric Weitz , Martina Summer-Kutmon , and Isabel Wassink

Activity

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Cited In

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Organisms

Homo sapiens

Communities

COVID-19

Annotations

Disease Ontology

COVID-19 severe acute respiratory syndrome viral infectious disease

Pathway Ontology

regulatory pathway altered ubiquitin/proteasome degradation pathway disease pathway

Cell Type Ontology

peripheral blood mononuclear cell

Participants
Query Drugst.One

Label Type Compact URI Comment
Pevonedistat Metabolite wikidata:Q25100575
NAE1 GeneProduct ensembl:ENSG00000159593
UBA3 GeneProduct ensembl:ENSG00000144744
CUL2 GeneProduct ensembl:ENSG00000108094
ELOC GeneProduct ensembl:ENSG00000154582
ELOB GeneProduct ensembl:ENSG00000103363
RBX1 GeneProduct ensembl:ENSG00000100387
E2 GeneProduct ensembl:ENSG00000067955
ZYG11B GeneProduct ensembl:ENSG00000162378
orf10 Protein wikidata:Q89227548

References

  1. The Caenorhabditis elegans cell-cycle regulator ZYG-11 defines a conserved family of CUL-2 complex components. Vasudevan S, Starostina NG, Kipreos ET. EMBO Rep. 2007 Mar;8(3):279–86. PubMed Europe PMC Scholia
  2. Pharmacological targets in the ubiquitin system offer new ways of treating cancer, neurodegenerative disorders and infectious diseases. Edelmann MJ, Nicholson B, Kessler BM. Expert Rev Mol Med. 2011 Nov 17;13:e35. PubMed Europe PMC Scholia
  3. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, et al. Nature. 2020 Jul;583(7816):459–68. PubMed Europe PMC Scholia